Sodium hydride → Ethyl 2-{[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino}-3-nitrobenzoate

HRID 1737876Notes

Reaction equation

HRID 1737876 reaction equation
C(O[C:6]([NH:8][C:9]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:10]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=O)(C)(C)C.[H-].[Na+].[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:40]=[CH:39][C:36](CBr)=[CH:35][CH:34]=1)#[N:26]>O1CCCC1.FC(F)(F)C(O)=O.C(Cl)Cl.[I-].[K+]>[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[CH:40]=[CH:39][C:36]([CH2:6][NH:8][C:9]2[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:35][CH:34]=1)#[N:26]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 12018930Ethyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate

Product 1

HCID 12018931Ethyl 2-{[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino}-3-nitrobenzoateYield 85.4%

Reagents, catalysts & solvents 4

HCID 4875Potassium IodideCatalystHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2 -t-butoxycarbonylamino-3-nitrobenzoate (20 g) in tetrahydrofuran (50 ml) was added, while stirring under ice-cooling, sodium hydride (60% dispersion in mineral oil, 2.8 g). The mixture was stirred at room temperature for 20 minutes and to the mixture were then added 4 -(2-cyanophenyl)benzyl bromide (18 g) and potassium iodide (360 mg), followed by heating for 10 hours under reflux. The solvent was evaporated to dryness and the residue was partitioned between water (250 ml) and ether (200 ml). The organic layer was washed with water, dried and concentrated to give a yellow syrup. The syrup was dissolved in a mixture of trifluoroacetic acid (60 ml) and methylene chloride (40 ml) and the solution was stirred for one hour at room temperature. The reaction mixture was concentrated to dryness and to the residue was added ethyl ether (200 ml) to give crystals. The crystals were collected by filtration, washed with ether to give pale yellow crystals (22.1 g, 85%), m.p. 118-119° C.

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at room temperature for 20 minutes and to the mixture
  3. temperatureby heating for 10 hours
  4. temperatureunder reflux
  5. customThe solvent was evaporated to dryness
  6. customthe residue was partitioned between water (250 ml) and ether (200 ml)
  7. washThe organic layer was washed with water
  8. customdried
  9. concentrationconcentrated
  10. customto give a yellow syrup
  11. stirringthe solution was stirred for one hour at room temperature
  12. concentrationThe reaction mixture was concentrated to dryness and to the residue
  13. additionwas added ethyl ether (200 ml)
  14. customto give crystals
  15. filtrationThe crystals were collected by filtration
  16. washwashed with ether

Sources & evidence

ORD record
ord-922acc5af0ad448fb269f7961a752ab6
Source dataset
uspto-grants-1999_10
Patent number
US05962491

Reaction notes

Loading…